Recent advances in MeCP2 structure and function.
Recent advances in MeCP2 structure and function.
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DOI：
10.1139/o08-115
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发表时间：
2009-02
期刊：
影响因子：
--
通讯作者：
Hansen JC
中科院分区：
文献类型：
--
作者：
Hite KC;Adams VH;Hansen JC
甲基DNA结合蛋白2（MeCP2）的突变导致神经发育障碍Rett综合征（RTT）。天然MeCP 2蛋白在细胞中发挥作用的机制尚不清楚。历史上，MeCP2已被表征为具有2个功能结构域的近端基因沉默子：甲基DNA结合结构域和转录抑制结构域。然而，一些新的数据表明MeCP2的结构和功能关系更加复杂。在这篇综述中，我们首先讨论了最近的研究，有先进的理解的基本结构生物化学的MeCP2。接下来是基于细胞的实验分析，表明MeCP2是转录的调节剂，而不是严格的沉默剂。新数据确定MeCP2是一种多功能核蛋白，在染色质结构、RNA剪接调控和活性转录中具有潜在的重要作用。最后，我们通过讨论结构域特异性突变和RTT病理之间的临床相关性来强调MeCP2的所有结构域都是正确介导完整蛋白质的细胞功能所必需的。
Mutations in methyl DNA binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome (RTT). The mechanism(s) by which the native MeCP2 protein operates in the cell are not well understood. Historically, MeCP2 has been characterized as a proximal gene silencer with 2 functional domains: a methyl DNA binding domain and a transcription repression domain. However, several lines of new data indicate that MeCP2 structure and function relationships are more complex. In this review, we first discuss recent studies that have advanced understanding of the basic structural biochemistry of MeCP2. This is followed by an analysis of cell-based experiments suggesting MeCP2 is a regulator, rather than a strict silencer, of transcription. The new data establish MeCP2 as a multifunctional nuclear protein, with potentially important roles in chromatin architecture, regulation of RNA splicing, and active transcription. We conclude by discussing clinical correlations between domain-specific mutations and RTT pathology to stress that all structural domains of MeCP2 are required to properly mediate cellular function of the intact protein.